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Biomedical subjects

Ya-Ting Chen

Publications and source records attributed to Ya-Ting Chen.

15 recordsLinked to original sources

Complex mutation patterns of epidermal growth factor receptor gene associated with variable responses to gefitinib treatment in patients with non-small cell lung cancer.

Mutational analysis was performed in the kinase domain (exons 18-21) of the EGFR gene on tumor tissues of 65 non-small cell lung cancer (NSCLC) patients who had received gefitinib monotherapy. The association between EGFR gene mutation, gefitinib treatment response, and the overall survival were evaluated. In total, EGFR mutations with complex patterns were identified in 32 tumors. The overall mutation rate was 49.2% (32/65). Twenty of the 32 patients were responders, 10 non-responders, and 2 not assessable. The most common mutation in non-responders was L858R. Gefitinib responsiveness was only significantly associated with EGFR mutation and adenocarcinoma. The median survival for responder (15.5 months) was much longer than non-responder (9.23 months), though the difference only had marginal significance (p=0.056). The difference of overall survival between patients with and without EGFR mutation was non-significant (p=0.7819), mainly due to the short survival of the non-responders with EGFR mutations (median survival=6.2 months). Our study revealed that the response to gefitinib treatment in NSCLC patients with EGFR mutations could be quite variable even for the same EGFR mutation type. An analysis of the various EGFR mutations and the response patterns was also performed and compared with recently published reports on EGFR mutation and gefitinib responsiveness.

Adenocarcinoma↗

Postoperative nausea and vomiting following inpatient surgeries in a teaching hospital: a retrospective database analysis.

OBJECTIVE: To report the incidence of postoperative nausea and vomiting (PONV), to describe the use of anti-emetics both for the prophylaxis and treatment of PONV, and to assess resource utilization and duration of post-anesthesia care unit (PACU) stay. RESEARCH DESIGN AND METHODS: We retrieved data from the Duke Anesthesia Peri-operative database. We included adult patients, who underwent inpatient surgery under general anesthesia with inhaled agents between January 2004 and February 2005, and had two or more risk factors for PONV documented preoperatively (female, previous history of PONV or motion sickness, non-smoker or use of postoperative opioid). Data on the use of prophylactic anti-emetics, the incidence of PONV, nausea scores, pain scores, and the use of rescue anti-emetics in PACU and in the period between PACU discharge and 24 h after surgery were recorded. Resource utilization and cost assessment was performed from the perspective of the hospital and included length and direct cost of PACU stay, as well as the acquisition costs of rescue anti-emetics in PACU. Descriptive statistics were used to summarize the demographic characteristics of patients. For group comparisons, data were analyzed with the t-test for continuous data, and the Chi-square test for categorical data. Multiple linear regression models were used to evaluate the association between PONV and PACU length of stay adjusting for confounding factors. RESULTS: A total of 3641 patients were included in the analysis. Of those, 2869 (79%) received prophylactic anti-emetics. In the PACU, nausea and vomiting were reported in 16% and 3% of the patients, respectively. Rescue anti-emetics were given to 26% of all patients. The incidence of vomiting was significantly less in patients who received PONV prophylaxis (p = 0.03). In multiple linear regression models, the duration of PACU stay was longer by a mean of 25 min in patients who experienced PONV or received rescue anti-emetics in PACU (p < 0.0001) despite the fact that the duration of surgery was shorter by a mean of 24 min in this group of patients (p < 0.0001). Following PACU discharge, 40% of patients reported nausea, vomiting or needed rescue anti-emetics. PONV was associated with significantly increased resource utilization and costs of PACU stay (p < 0.0001). Emesis was associated with greater incremental cost (138 US dollars) than nausea (85 US dollars), mainly from the longer duration of PACU stay. CONCLUSIONS: PONV remain a significant problem postoperatively and often persists beyond PACU discharge. The presence of PONV is associated with increased length of PACU stay and greater resource utilization and costs.

Adult↗

Interactive voice response telephone calls to enhance bone mineral density testing.

OBJECTIVE: Bone mineral density (BMD) testing is a key tool used to diagnose and treat osteoporosis. We assessed the rate of scheduling BMD tests among health plan members at risk for osteoporosis who received interactive voice response (IVR) calls. STUDY DESIGN: Cohort study. METHODS: Study patients included persons age 45 years with either a prior fracture or 90 days of glucocorticoid use and all women age 65 years during the 2-year baseline period. The IVR call provided educational content and then offered members an opportunity to transfer to schedule a BMD test. The primary outcome was scheduling a BMD test. RESULTS: We targeted 1402 health plan members, and 708 (50%) were successfully contacted. Of 54 patients who transferred to schedule a BMD test, only 3 actually did so. Because so few patients scheduled a BMD test, predictors of transfer were examined as a secondary end point. In a multivariate model, only self-reported intention to schedule a BMD test was a significant predictor (odds ratio = 4.4, 95% confidence interval = 2.2, 8.8). Members' age, sex, history of a prior fracture, self-report of a BMD test in the previous 2 years, acknowledgement of barriers to BMD testing, and discussion of BMD testing with one's physician were not related to transferring to schedule a BMD test. CONCLUSION: A letter and an IVR call prompted few to schedule a BMD test. More interventions to improve BMD testing should be developed and tested.

Aged↗

Inhibition of amyloid fibril formation of beta-amyloid peptides via the amphiphilic surfactants.

Beta-amyloid peptide (A beta) is the major proteinacious constituent of senile plaques in Alzheimer's disease and is believed to be responsible for the neurodegeneration process associated with the disease. While the actual size of the aggregated species responsible for A beta neurotoxicity and fibrillogenesis mechanism(s) remain unknown, retardation of A beta aggregation still holds assurance as an effective strategy in reducing A beta-elicited toxicity. The research presented here is aimed at examining the inhibitory effect of two amphiphilic surfactants, di-C6-PC and di-C7-PC, on the in vitro fibrillogenesis process of A beta(1--40) peptides at physiological pH (pH 7.2). Using ThT-induced fluorescence, turbidity, Congo red binding, and circular dichroism spectroscopy studies, our research demonstrated that the inhibition of A beta(1--40) fibril formation was di-C6-PC and di-C7-PC concentration-dependent. The best inhibitory action on fibril formation was observed when A beta was incubated with di-C7-PC at 100 microM over time. We believe that the outcome from this work will aid in the development and/or design of potential inhibitory agents against amyloid formation associated with Alzheimer's and other amyloid diseases.

Amyloid beta-Peptides↗

Prevalence of vitamin D inadequacy in a minimal trauma fracture population.

OBJECTIVE: The purpose of this analysis was to report the prevalence of vitamin D inadequacy in a population of adults with minimal trauma fractures. RESEARCH DESIGN AND METHODS: 82 adults (ages 52-97 with 63% age 80+) consecutively hospitalized with hip and extremity fractures between August 2001 and January 2002 were recruited from two St. Paul, MN hospitals. Patients came from independent living and assisted living facilities. Demographics, medical history and vitamin D supplementation were obtained by the medical record and self-report. Blood specimens were collected during hospitalization within 48 hours of admission. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were assessed using Diasorin 25-hydroxyvitamin D radioimmunoassay kit (RIA) at Mayo Clinic, Rochester, MN. Results were available for 78 patients and are included in the current analysis. RESULTS: Patients were 99% Caucasian, 63% >/=80 years and 78% female. 97% were admitted due to hip fracture. On admission, 50% reported using at least 400 IU per day of vitamin D through supplements (including multivitamins) and 13% of all patients were taking osteoporosis medication (3 estrogen, 5 alendronate, 1 etidronate, 1 raloxifene). The mean 25(OH)D concentration was 14.2 (SD 6.6) with a range of 5-39 ng/mL (8-38 ng/mL wintertime vales in Rochester, MN). All but two of the 78 patients (97.4%) had 25(OH)D concentrations < 30 ng/mL and the majority (81%) of the patients had 25(OH)D concentrations < 20 ng/mL, including 21% < 9 ng/mL. Mean 25(OH)D concentrations were not substantially different by gender, age, or osteoporosis medication use. Patients who reported vitamin D supplementation >/= 400 IU/day had significantly greater mean 25(OH)D concentrations, albeit suboptimal, compared to those who did not (16.4 vs. 13.7 ng/mL; p = 0.002). CONCLUSIONS: Nearly all patients in this study hospitalized for fracture had vitamin D inadequacy. Significant opportunity exists to ensure adequate and persistent vitamin D intake in a high risk fracture patient population.

Aged↗

High frequency of epidermal growth factor receptor mutations with complex patterns in non-small cell lung cancers related to gefitinib responsiveness in Taiwan.

PURPOSE: Epidermal growth factor receptor (EGFR) mutations related to gefitinib responsiveness in non-small cell lung cancer have been found recently. Detection of EGFR mutations has become an important issue for therapeutic decision-making in non-small cell lung cancer. EXPERIMENTAL DESIGN: Mutational analysis of the kinase domain of EGFR coding sequence was done on 101 fresh frozen tumor tissues from patients without prior gefitinib treatment and 16 paraffin-embedded tumor tissues from patients treated with gefitinib. Detection of phosphorylated EGFR by immunoblot was also done on frozen tumor tissues. RESULTS: The 101 non-small cell lung cancer tumor specimens include 69 adenocarcinomas, 24 squamous cell carcinomas, and 8 other types of non-small cell lung cancers. Mutation(s) in the kinase domain (exon 18 to exon 21) of the EGFR gene were identified in 39 patients. All of the mutations occurred in adenocarcinoma, except one that was in an adenosquamous carcinoma. The mutation rate in adenocarcinoma was 55% (38 of 69). For the 16 patients treated with gefitinib, 7 of the 9 responders had EGFR mutations, and only 1 of the 7 nonresponders had mutations, which included a nonsense mutation. The mutations seem to be complex in that altogether 23 different mutations were observed, and 9 tumors carried 2 mutations. CONCLUSIONS: Data from our study would predict a higher gefitinib response rate in lung adenocarcinoma patients in Chinese and, possibly, other East Asian populations. The tight association with adenocarcinoma and the high frequency of mutations raise the possibility that EGFR mutations play an important role in the tumorigenesis of adenocarcinoma of lung, especially in East Asians.

Adenocarcinoma↗

Bone mineral density thresholds for pharmacological intervention to prevent fractures.

BACKGROUND: Treatment intervention thresholds for prevention of osteoporotic fractures can be derived from reports from the World Health Organization (diagnostic criteria) and National Osteoporosis Foundation (treatment criteria). It is not known how well these thresholds work to identify women who will fracture and are therefore candidates for treatment interventions. We used data from the National Osteoporosis Risk Assessment (NORA) to examine the effect of different treatment thresholds on fracture incidence and numbers of women with fractures within the year following bone mineral density measurement. METHODS: The study comprised 149 524 white postmenopausal women aged 50 to 104 years (mean age, 64.5 years). At baseline, bone mineral density was assessed by peripheral bone densitometry at the heel, finger, or forearm. New fractures during the next 12 months were self-reported. RESULTS: New fractures were reported by 2259 women, including 393 hip fractures; only 6.4% had baseline T scores of -2.5 or less (World Health Organization definition for osteoporosis). Although fracture rates were highest in these women, they experienced only 18% of the osteoporotic fractures and 26% of the hip fractures. By National Osteoporosis Foundation treatment guidelines, 22.6% of the women had T scores of 2.0 or less, or -1.5 or less with 1 or more clinical risk factors. Fracture rates were lower, but 45% of osteoporotic fractures and 53% of hip fractures occurred in these women. CONCLUSIONS: Using peripheral measurement devices, 82% of postmenopausal women with fractures had T scores better than -2.5. A strategy to reduce overall fracture incidence will likely require lifestyle changes and a targeted effort to identify and develop treatment protocols for women with less severe low bone mass who are nonetheless at increased risk for future fractures.

Age Distribution↗

An approach to identifying osteopenic women at increased short-term risk of fracture.

BACKGROUND: Identification and management of women to reduce fractures is often limited to T scores less than -2.5, although many fractures occur with higher T scores. We developed a classification algorithm that identifies women with osteopenia (T scores of -2.5 to -1.0) who are at increased risk of fracture within 12 months of peripheral bone density testing. METHODS: A total of 57 421 postmenopausal white women with baseline peripheral T scores of -2.5 to -1.0 and 1-year information on new fractures were included. Thirty-two risk factors for fracture were entered into a classification and regression tree analysis to build an algorithm that best predicted future fracture events. RESULTS: A total of 1130 women had new fractures in 1 year. Previous fracture, T score at a peripheral site of -1.8 or less, self-rated poor health status, and poor mobility were identified as the most important determinants of short-term fracture. Fifty-five percent of the women were identified as being at increased fracture risk. Women with previous fracture, regardless of T score, had a risk of 4.1%, followed by 2.2% in women with T scores of -1.8 or less or with poor health status, and 1.9% for women with poor mobility. The algorithm correctly classified 74% of the women who experienced a fracture. CONCLUSIONS: This classification tool accurately identified postmenopausal women with peripheral T scores of -2.5 to -1.0 who are at increased risk of fracture within 12 months. It can be used in clinical practice to guide assessment and treatment decisions.

Age Distribution↗

Predictive value of low BMD for 1-year fracture outcomes is similar for postmenopausal women ages 50-64 and 65 and Older: results from the National Osteoporosis Risk Assessment (NORA).

UNLABELLED: The relationship of low bone mass and fracture in younger postmenopausal women has not been extensively studied. In a large cohort of postmenopausal women > or =50 years of age, we found the relationship of BMD measured at peripheral sites and subsequent 1-year fracture risk to be similar between women <65 and those > or =65 years of age. INTRODUCTION: Low bone mass and fractures are prevalent in older postmenopausal women. However, the frequency of low bone mass and fracture in younger postmenopausal women has not been studied extensively. There are very limited data regarding the association between BMD measurements and fractures in postmenopausal women who are between the ages of 50 and 64. MATERIALS AND METHODS: In the National Osteoporosis Risk Assessment (NORA) we studied the frequency of low bone mass and its association with fracture in women 50-64 years of age in comparison with women > or =65 of age. NORA enrolled 200,160 postmenopausal women > or =50 years of age who had no prior diagnosis of osteoporosis. Baseline BMD was measured at the heel, forearm, or finger. A 1-year follow-up survey requesting incident fractures since baseline was completed by 163,935 women, 87,594 (53%) of whom were 50-64 years of age. The association between BMD and fracture was assessed using logistic regression, adjusted for important covariates. RESULTS: Thirty-one percent of women 50-64 years of age had low bone mass (T scores < or = -1.0) compared to 62% of women > or =65 years of age. During the first year of follow-up, 2440 women reported fractures of wrist/forearm, rib, spine, or hip, including 440 hip fractures. Nine hundred four women 50-64 years of age reported fractures, including 86 hip fractures, accounting for 37% of fractures and 20% of hip fractures reported in the entire NORA cohort. Relative risk for osteoporotic fracture was 1.5 for each SD decrease in BMD for both the younger and older groups of women. CONCLUSION: Low BMD in younger postmenopausal women 50-64 years of age showed a 1-year relative risk of fracture similar to that found in women > or =65 years of age.

Age Factors↗

Rapid loss of hip fracture protection after estrogen cessation: evidence from the National Osteoporosis Risk Assessment.

OBJECTIVE: Since the findings from the Women's Health Initiative became available in July 2002, millions of women have discontinued postmenopausal hormone therapy (HT). The objective of this study was to evaluate the association between HT cessation and hip fracture risk. METHODS: Women who participated in the National Osteoporosis Risk Assessment and completed the 12-month follow-up survey were studied. All participants were aged at least 50 years, were postmenopausal, and had no previous diagnosis of osteoporosis. Baseline and 12-month follow-up questionnaires assessed use of HT and incident fractures. Of the 140,584 women in this study, 269 reported an incident hip fracture. A logistic regression model was used to assess association between HT use and incident hip fracture, controlling for potential confounders. RESULTS: Consistent with the Women's Health Initiative, women in National Osteoporosis Risk Assessment who were currently on HT had a 40% lower incidence of hip fractures compared with those who never used HT. Women who stopped using HT more than 5 years earlier had similar hip fracture risk to never users, as expected. However, surprisingly, women who had discontinued HT within the previous 5 years had an increased hip fracture odds ratio of 1.65 (95% confidence interval 1.05, 2.59) relative to never users of HT. CONCLUSION: Postmenopausal women who have discontinued HT within the past 5 years have a risk for hip fracture that is at least as high as that in women who have never used HT. LEVEL OF EVIDENCE: II-2

Aged↗

Evaluation and management of osteoporosis following hospitalization for low-impact fracture.

OBJECTIVE: To evaluate the pattern of osteoporosis evaluation and management in postmenopausal women who present with low-impact (minimal trauma) fracture. DESIGN: Retrospective chart review of patients admitted with a fracture in the absence of trauma or bone disease. Telephone follow-up survey was conducted at 12 months after discharge to collect information on physician visits, pharmacological therapies for osteoporosis, functional status, and subsequent fractures. PATIENTS/PARTICIPANTS: Postmenopausal women admitted to a hospital in St. Paul, Minnesota between June 1996 and December 1997 for low-impact fractures were identified. Low-impact fracture was defined as a fracture occurring spontaneously or from a fall no greater than standing height. Retrospective review of 301 patient medical records was conducted to obtain data on pre-admission risk factors for osteoporosis and/or fracture, and osteoporosis-related evaluation and management during the course of hospitalization. Follow-up 1 year after the incident fracture was obtained on 227 patients. MEASUREMENTS AND MAIN RESULTS: Two hundred twenty-seven women were included in the study. Osteoporosis was documented in the medical record in 26% (59/227) of the patients at hospital discharge. Within 12 months of hospital discharge, 9.6% (22/227) had a bone mineral density test, and 26.4% (60/227) were prescribed osteoporosis treatment. Of those who were prescribed osteoporosis treatment, 86.6% (52/60) remained on therapy for 1 year. Nineteen women suffered an additional fracture. Compared to women without a prior fracture, women with at least 1 fracture prior to admission were more likely to have osteoporosis diagnosed and to receive osteoporosis-related medications. CONCLUSION: Despite guidelines that recommend osteoporosis evaluation in adults experiencing a low-trauma fracture, we report that postmenopausal women hospitalized for low-impact fracture were not sufficiently evaluated or treated for osteoporosis during or after their hospital stay. There are substantial opportunities for improvement of care in this high-risk population to prevent subsequent fractures.

Aged↗

Management of osteoporosis in women aged 50 and older with osteoporosis-related fractures in a managed care population.

This study describes the pattern of evaluation and management of osteoporosis in women aged 50 and older following an osteoporosis-related fracture, conducted as a retrospective cohort study using the administrative claims database of a managed care organization. Subjects were women, aged 50 years and older, with at least one osteoporosis-related fracture in the years 1996-1998 who were continuously enrolled in the system's health plan for at least 6 months prior to and post-fracture. Bone mineral density (BMD) testing, diagnosis of osteoporosis, and treatment with any Food and Drug Administration-approved medication for osteoporosis were identified using CPT, ICD-9, and National Drug Codes for the 6-month post-fracture period. There were 658 women with an osteoporosis-related fracture: 189 (29%) hip fractures, 226 (34%) wrist fractures, 127 (19%) vertebral fractures, and 116 (18%) rib fractures. In the post-fracture period, 46 (7%) underwent BMD testing, 153 (23%) had a diagnosis of osteoporosis, and 220 (31%) were treated with a medication approved for the prevention or treatment of osteoporosis. Of the 220 women with medication claims, 124 (56%) were for estrogen, and 96 (44%) were for other antiresorptive agents. Of the 507 women who did not have medication claims during the 6 months prior to the fracture, only 17% had new fills after the fracture. Management of osteoporosis in women aged 50 and older with fractures was inadequate, despite the high risk of subsequent fractures and recommendations that osteoporosis be the presumptive diagnosis. Significant opportunity exists for improvement in assuring post-fracture followup care.

Aged↗

Evaluation of decision rules to identify postmenopausal women for intervention related to osteoporosis.

Decision rules for intervention that utilize screening tools for bone mineral density (BMD) testing and incorporating the BMD findings and other risk factors to identify high-risk women to prevent fracture have not been evaluated. We examine the sensitivity and specificity of decision rules for intervention based on two pre-BMD screening tools: Simple Calculated Osteoporosis Risk Estimation (SCORE) and a Study of Osteoporotic Fractures (SOF)-based tool. Women 60 years of age and older without previous osteoporosis diagnosis were randomly selected from a managed care population and invited to receive a BMD test. Four hundred sixteen women had complete information and were included in the study. Women were classified as high risk requiring intervention using three different criteria: World Health Organization (t-score -2.5 or less), National Osteoporosis Foundation (t-score -2.0 or less, or -1.5 or less with one or more risk factors), and the SOF-based criteria (prior fracture; or age 60-64 with t-score less than -2.5 or age 65 or older with z-score less than -0.43 and five or more risk factors). SCORE identified 82% of the women as appropriate for BMD testing, whereas the SOF-based tool identified 26%. Sensitivity and specificity were 89.8%-96.5% and 23.8%-34.8%, respectively, for the decision rule using SCORE as the screening tool and 30.5%-84.9% and 76.0%-95.8%, respectively, for the decision rule based on SOF screening criteria. SCORE correctly identified more women who were at high risk for intervention, whereas the SOF-based tool correctly identified more women who do not meet intervention criteria. The appropriate selection of a screening tool depends upon the objective for intervention and trade-off between not identifying women for BMD testing who are at high risk and identifying more women for BMD testing who are at low risk.

Aged↗

Prediction of fracture risk in postmenopausal white women with peripheral bone densitometry: evidence from the National Osteoporosis Risk Assessment.

Low bone mineral density (BMD) is a risk factor for fracture. Although the current "gold standard" test is DXA of the hip and spine, this method is not universally available. No large studies have evaluated the ability of new, less expensive peripheral technologies to predict fracture. We studied the association between BMD measurements at peripheral sites and subsequent fracture risk at the hip, wrist/forearm, spine, and rib in 149,524 postmenopausal white women, without prior diagnosis of osteoporosis. At enrollment, each participant completed a risk assessment questionnaire and had BMD testing at the heel, forearm, or finger. Main outcomes were new fractures of the hip, wrist/forearm, spine, or rib within the first 12 months after testing. After 1 year, 2259 women reported 2340 new fractures. Based on manufacturers' normative data and multivariable adjusted analyses, women who had T scores < or = -2.5 SD were 2.15 (finger) to 3.94 (heel ultrasound [US]) times more likely to fracture than women with normal BMD. All measurement sites/devices predicted fracture equally well, and risk prediction was similar whether calculated from the manufacturers' young normal values (T scores) or using SDs from the mean age of the National Osteoporosis Risk Assessment (NORA) population. The areas under receiver operating characteristic (ROC) curves for hip fracture were comparable with those published using measurements at hip sites. We conclude that low BMD found by peripheral technologies, regardless of the site measured, is associated with at least a twofold increased risk of fracture within 1 year, even at skeletal sites other than the one measured.

Absorptiometry, Photon↗

Recency and duration of postmenopausal hormone therapy: effects on bone mineral density and fracture risk in the National Osteoporosis Risk Assessment (NORA) study.

OBJECTIVES: Results from the Women's Health Initiative showed that postmenopausal hormone replacement therapy (HRT) prevents fractures but has an overall unfavorable risk:benefit ratio, leading to the recommendation that HRT be used only for women with troublesome menopause symptoms, and for as short a time as possible. This recommendation has important implications for the timing and duration of HRT and the prevention of osteoporosis. The large number of women participating in the National Osteoporosis Risk Assessment (NORA) program provided the opportunity to evaluate bone mineral density (BMD) and 1-year fracture risk in analyses stratified by duration and recency of HRT. DESIGN: Participants were 170,852 postmenopausal women aged 50 to 104, without known osteoporosis, who were recruited from primary physicians offices across the US. BMD was measured at one of four peripheral sites, and the 1-year risk of osteoporotic fracture was assessed by questionnaire. RESULTS: At baseline, current HRT users had the highest T-scores at every age. Among current hormone users, women who had used HRT longest had the highest BMD levels. Women who had stopped HRT more than 5 years previously, regardless of duration of use, had T-scores similar to never-users. Current but not past hormone use at baseline was associated with a 25% to 29% lower risk of osteoporotic fracture (P < 0.0001) in 1 year, compared with nonusers. These findings were independent of age, ethnicity, body mass index, lifestyle, years postmenopausal, and site of BMD measurement. CONCLUSIONS: We conclude that postmenopausal BMD and fracture are closely associated with current, but not prior, HRT use. Use of HRT for 5 years or less, as proposed for treatment of symptomatic women during menopause transition, is unlikely to preserve bone or significantly reduce fracture risk in later years.

Aged↗